Microbiome Immunotherapy Toxicity and Response Evaluation

Inclusion Criteria for cancer patients:

• Signed informed consent

• Aged ≥18 years old

• Histological or cytological confirmation of invasive malignancy

• Due to commence palliative, adjuvant or neoadjuvant systemic therapy including an anti-PD-(L)1 antibody +/- anti-CTLA-4 antibody

• Patients with unresectable disease must have radiologically and/or clinically measurable disease, by RECIST version 1.1; target lesions must not have been previously irradiated; baseline tumour assessments must be performed within 45 days prior to starting immune checkpoint inhibitor treatment

• Received no prior immune checkpoint inhibitors (previous treatment with other types of anti-cancer therapy is determined by patient cohort; for patients with unresectable disease, prior adjuvant therapy with immune checkpoint inhibitor(s) is allowed).

• Willing and able to comply with scheduled visits, treatment plans, sample collections and other study procedures

Exclusion Criteria for cancer patients:

• Other invasive malignancies diagnosed within the last year which are not fully resected, or in complete remission, or for which additional therapy is required

• Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk, or interfere with their ability to comply with the study. Examples may include, but are not limited to:

• Patients with uncontrolled ischaemic heart or other cardiovascular event (e.g. myocardial infarction, new angina, stroke, transient ischaemic attack, or new congestive cardiac failure) within the last 6 months

• Presence of active infection

• Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C

• Current active, severe, or uncontrolled autoimmune condition, including but not limited to Crohn's disease and ulcerative colitis.

• Women who are pregnant, plan to become pregnant or are lactating during the study period.

• Requirement for non-physiological dose of oral steroids, or regular use of any other immunosuppressive agents; less than 10mg prednisolone or equivalent doses are allowed. Use of inhaled or topical steroids is allowed.

Household control eligibility requirements:

Confirmation of suitability to be a household control participant will be determined by completing a self-assessed questionnaire either at home or in clinic.

Household controls must:

• NOT have had any gastrointestinal infections i.e., parasites, viruses or diarrhoeal episodes during the last 6 months.

• NOT have taken antibiotics for at least 6 months

• NOT have or be recovering from any chronic intestinal disease such as:

• Crohn's disease

• Ulcerative colitis

• Coeliac disease

• Irritable bowel syndrome

• Stomach ulcers

• NOT have a chronic autoimmune disease or significant allergies e.g., multiple sclerosis, asthma requiring regular medication, psoriasis.

• NOT have and NOT be recovering from any form of cancer.

• NOT take proton pump inhibitors, steroids, other non-steroidal anti-inflammatory drugs such as ibuprofen or aspirin.

• NOT had requirement to be hospitalised for treatment of COVID-19

In addition, household controls must sign informed consent and be aged ≥18 years old.